The proposed research project will investigate how human salivary lysozyme, histidine-rich polypeptides and penicillin interact with the cell envelope of Streptococcus mutans and potentially alter the pathogenicity of this oral bacterium (i.e., its ability to adhere to teeth, synthesize dextrans and metobolize sugars). The novel approach here involves comparisons of responses of intact cells and wall-free protoplasts of s. mutans BHT after exposur to salivary componenrs. This will allow a differentiation between the specific reactions of the cell membrane and wall with these exogenous molecules. Human salivary lysozyme and histidine-rich polypeptides will be purified according to published protocols and then incubated with whole cells and protoplasts of s. mutans BHT. Both cell types will be examined for alterations in their physicochemical composition as a result of exposure to these molecules. Particular attention will be paid to membrane changes which effect 1) viability: such as leakage of cytoplasmic components, inhibition of enzyme activities involved in sugar transport and energy production, or inducion of gross lysis; 2) growth; such as alterations in the concentration of membrane components including lipoteichoic acids, intracellular storage polysaccharides and ability to synthesize cellular macromolecules; and 3) adherence: such as glycosyl transferase activity and ability to adhere to hydroxylapatite. in addition, studies with inhibitors of cell wall synthesis will be performed to elucidate the non-lysis (tolerant) behavior of s. mutans and the secondary inhibitions of RNA and protein synthesis which have been observed after exposure of cells to penicillin. These studies will lead to an increased understanding of how S. mutans interacts with specific molecules to which it is exposed in the oral cavity and to molecules which may potentially inhibit its adherence and growth.